Articles about diseases

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“Impact of the Addition of Carboplatin and/or Bevacizumab to Neoadjuvant Once-Per-Week Paclitaxel Followed by Dose-Dense Doxorubicin and Cyclophosphamide on Pathologic Complete Response Rates in Stage II to III Triple-Negative Breast Cancer: CALGB 40603 (Alliance)” was accepted as a rapid publication and published online this month by the Journal of Clinical Oncology. It will come out in print in September.

Because of its rapid growth rate, many women with triple-negative breast cancer receive chemotherapy to try to shrink it before undergoing surgery. With the standard treatment, the cancer is eliminated from the breast and lymph nodes in the armpit before surgery in about one third of women. This is referred to as a pathologic complete response (pCR). In patients who achieve pCR, the cancer is much less likely to come back, spread to other parts of the body, and cause the patient’s death than if the cancer survives the chemotherapy.

Sikov and his collaborators studied the addition of other drugs — carboplatin and/or bevacizumab — to the standard treatment regimen to see if they could increase response rates. More than 440 women from cancer centers across the country enrolled in this randomized clinical trial.

“Adding either of these medications significantly increased the percentage of women who achieved a pCR with the preoperative treatment. We hope that this means fewer women will relapse and die of their cancer, though the study is not large enough to prove this conclusively. Of the two agents we studied, we are more encouraged by the results from the addition of carboplatin, since it was associated with fewer and less concerning additional side effects than bevacizumab,” Sikov explains.

“More studies are planned to confirm the role of carboplatin in women with triple-negative breast cancer, and also to see if we can better identify which of these patients are most likely to benefit from its use. Until we have those results, medical oncologists who treat women with triple-negative breast cancer will have to decide whether the potential benefits of adding carboplatin outweigh its risks for each individual patient.”

Triple-negative breast cancer accounts for 15 to 20 percent of invasive breast cancers diagnosed in the United States each year, and is more common in younger women, African-Americans, Hispanics, and BRCA1-mutation carriers. With no identified characteristic molecular abnormalities that can be targeted with medication, the current standard of treatment is chemotherapy.

“Overall prognosis for women with this type of breast cancer remains inferior to that of other breast cancer subtypes, with higher risk of early relapse,” Sikov says.

The study evaluated two groups of 31 men with prostate cancer that had spread and whose blood levels of prostate-specific antigen (PSA) were still rising despite low testosterone levels. Investigators gave each man either enzalutamide (Xtandi) or abiraterone (Zytiga) and tracked whether their PSA levels continued to rise, an indication that the drugs were not working. In the enzalutamide group, none of 12 patients whose blood samples tested positive for AR-V7 responded to the drug, compared with 10 responders among 19 men who had no AR-V7 detected. In the abiraterone group, none of six AR-V7-positive patients responded, compared with 17 responders among 25 patients lacking AR-V7.

Enzalutamide and abiraterone have been very successful in lengthening the lives of about 80 percent of patients with metastatic prostate cancer, says Emmanuel Antonarakis, M.D., assistant professor of oncology at Johns Hopkins, but the drugs do not work in the remaining 20 percent of patients.

“Until now, we haven’t been able to predict which patients will not respond to these therapies. If our results are confirmed by other researchers, a blood test could use AR-V7 as a biomarker to predict enzalutamide and abiraterone resistance, and let us direct patients who test positive for AR-V7 toward other types of therapy sooner, saving time and money while avoiding futile therapy,” says Antonarakis.

Prostate cancer thrives on male sex hormones (or “androgens”), including testosterone. Enzalutamide and abiraterone target proteins called androgen receptors and block the receptors’ ability to activate prostate cancer cells. AR-V7 is a shortened form of the androgen receptor that lacks a binding spot targeted by enzalutamide and abiraterone. With no binding spot for the two drugs, AR-V7 is free to manipulate prostate cancer cells’ genetic material, which makes the cancer cells grow and spread.

Antonarakis and his colleague Jun Luo, Ph.D., who first identified AR-V7 in 2008, also tracked patients’ progression-free survival (the length of time a patient lives with the disease but does not get worse) and overall survival. They found that, in men receiving enzalutamide, progression-free survival was 2.1 months in AR-V7-positive patients and 6.1 months in AR-V7-negative patients, while overall survival was 5.5 months in AR-V7-positive men and up to 9 months in AR-V7-negative men. Similarly, in men receiving abiraterone, progression-free survival was 2.3 months in AR-V7-positive patients and up to 6 months in AR-V7-negative patients, while overall survival was 10.6 months in AR-V7-positive men and up to 12 months in AR-V7-negative men. The investigators caution that most of the study patients had advanced disease and received multiple prior therapies, so their outcomes may not be generalizable to all men with prostate cancer.

“Patients whose blood samples contained AR-V7 got no benefit from either enzalutamide or abiraterone,” says Antonarakis. He adds that the shortened AR-V7 protein could appear in patients’ blood samples at the very start of therapy or acquired later, after therapy has begun. He says, “This test could be used before starting enzalutamide or abiraterone therapy, and if the test shows the presence of AR-V7, patients may opt for a different therapy. It could also be used to monitor patients receiving enzalutamide or abiraterone for AR-V7, providing an indication these drugs may not work for much longer.”

UCLA researchers found that men who aren’t well educated about their disease have a much more difficult time making treatment decisions, called decisional conflict, a challenge that could negatively impact the quality of their care and their long-term outcomes.

The study should serve as a wake-up call for physicians, who can use the findings to target men less likely to know a lot about their prostate cancer and educate them prior to their appointments so they’re more comfortable making treatment decisions, said study first author Dr. Alan Kaplan, a resident physician in the UCLA Department of Urology.

“For prostate cancer, there is no one right answer when it comes to treatment. It comes down to the right answer for each specific patient, and that is heavily dependent on their own personal preferences,” Kaplan said. “Men in general, and specifically economically disadvantaged men, have a hard time deciding what their preferences are, how they feel about any possible complications and what the future after treatment might be like. If you don’t know anything about your disease, you’ll have a really tough time making a decision.”

The findings from the one-year study appear in the early online edition of the peer-reviewed journal Cancer.

The research team surveyed 70 men at a Veterans Administration clinic who were newly diagnosed with localized prostate cancer and had enrolled in a randomized trial testing a novel shared decision-making tool. They collected baseline demographic and clinical such as age, race, education, co-existing medical conditions, relationship status, urinary and sexual dysfunction and their prostate cancer knowledge.

UCLA researchers talked one-on-one with the men after they had received their cancer diagnosis, but before they consulted with a physician. Median age of the men in the study was 63 years, 49% were African American and 70% reported an annual income of less than $30,000.

Kaplan said the team found that a low level of prostate cancer knowledge was associated with increased decisional conflict and higher uncertainty about what treatment to choose. Low levels of prostate cancer knowledge also were associated with lower perceived effectiveness — meaning the less they knew about their cancer, the less confidence they had that the treatment would be effective.

“Knowledge about prostate cancer is an identifiable target. Interventions designed to increase a patient’s comprehension of prostate cancer and its treatments may greatly reduce decisional conflict,” Kaplan said, adding that further study is needed to better characterize this relationship and identify effective targeted interventions.

“If you get shot in the gut, there aren’t many options. You go into the operating room to get fixed up,” he said. “With prostate cancer, there are lots of options and not all are right for everybody.”

Men with prostate cancer might need to decide between surgery versus radiation or opting for active surveillance, in which patients are monitored closely for changes in the progression of their cancer and are tested at regular intervals. Prostate cancers can also be treated implantable radioactive seeds or tumors may be burned or frozen as treatment.

Another benefit to reducing decisional conflict is that patients who feel comfortable with their decision may regret their decisions less down the line, Kaplan said. They’re less likely to sue their doctors and generally experience better outcomes.

“In a way, it’s like buying a car. You prepare, you read reports, do your homework,” Kaplan said. “If something goes wrong with the car, you feel OK because you knew what you were getting into. When patients take ownership of the decision-making process, their outcomes are better.”

Kaplan said economically disadvantaged men may be having more difficulty because they may not have as much experience negotiating the healthcare system and are less confident when communicating with doctors.

“Doctors, we know intuitively, should spend more time with their patients, especially when they’re making an important decision,” he said. “But all of us are challenged with the numbers of patients we must see in a day. If you know beforehand that a patient has a poor knowledge about his cancer, that’s someone you need to spend more time with.”

Doctors may also want to provide these patients with educational information before their consultation so they can begin to increase their prostate cancer knowledge, Kaplan said.

Prostate cancer is the most frequently diagnosed cancer in men aside from skin cancer. An estimated 233,000 new cases of prostate cancer will occur in the United States in 2014. Of those, nearly 30,000 men will die.